Pleiotropic effects of hemagglutinin amino acid substitutions of H5 influenza escape mutants

• Published in: Virology (New York, N.Y.) Vol. 447; no. 1; pp. 233 - 239
• Main Authors: Rudneva, Irina A, Timofeeva, Tatiana A, Ignatieva, Anna V, Shilov, Aleksandr A, Krylov, Petr S, Ilyushina, Natalia A, Kaverin, Nikolai V
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2013
• Subjects: 60 APPLIED LIFE SCIENCES; Amino Acid Substitution; AMINO ACIDS; Animals; ANTIBODIES; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Chick Embryo; Chickens; H5 hemagglutinin; HEAT; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; HYDROGEN 5; Hydrogen-Ion Concentration; IN VITRO; IN VIVO; INACTIVATION; Infectious Disease; INFLUENZA; Influenza A virus - genetics; Influenza A virus - physiology; Influenza escape mutants; Molecular Sequence Data; MONITORING; Mutant Proteins - genetics; Mutant Proteins - immunology; Mutant Proteins - metabolism; MUTANTS; Mutation, Missense; MUTATIONS; PH VALUE; Pleiotropic antibody-neutralizing mutations; RNA, Viral - genetics; Sequence Analysis, DNA; SPECIFICITY; Temperature; Virus Replication; Influenza escape mutants; Pleiotropic antibody-neutralizing mutations; H5 hemagglutinin
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2013.09.013

Abstract In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We examined pH optimum of fusion, temperatures of HA heat inactivation, and in vitro and in vivo replication kinetics of the previously obtained influenza H5 escape mutants. Our results showed that HA1 N142K mutation significantly lowered the pH of fusion optimum. Mutations of the escape mutants located in the HA lateral loop significantly affected H5 HA thermostability ( P <0.05). HA changes at positions 131, 144, 145, and 156 and substitutions at positions 131, 142, 145, and 156 affected the replicative ability of H5 escape mutants in vitro and in vivo , respectively. Overall, a co-variation between antigenic specificity and different HA phenotypic properties has been demonstrated. We believe that the monitoring of pleiotropic effects of the HA mutations found in H5 escape mutants is essential for accurate prediction of mutants with pandemic potential.